Structure of an extended-spectrum class A beta-lactamase from Proteus vulgaris K1

Journal of Molecular Biology
M NukagaJ R Knox

Abstract

The structure of a chromosomal extended-spectrum beta-lactamase (ESBL) having the ability to hydrolyze cephalosporins including cefuroxime and ceftazidime has been determined by X-ray crystallography to 1.75 A resolution. The species-specific class A beta-lactamase from Proteus vulgaris K1 was crystallized at pH 6.25 and its structure solved by molecular replacement. Refinement of the model resulted in crystallographic R and R(free) of 16.9 % and 19.3 %, respectively. The folding of the K1 enzyme is broadly similar to that of non-ESBL TEM-type beta-lactamases (2 A rmsd for C(alpha)) and differs by only 0.35 A for all atoms of six conserved residues in the catalytic site. Other residues promoting extended-spectrum activity in K1 include the side-chains of atypical residues Ser237 and Lys276. These side-chains are linked by two water molecules, one of which lies in the position normally filled by the guanidinium group of Arg244, present in most non-ESBL enzymes but absent from K1. The ammonium group of Lys276, ca 3.5 A from the virtual Arg244 guanidinium position, may interact with polar R2 substitutents on the dihydrothiazene ring of cephalosporins.

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Citations

Dec 17, 2009·Journal of the American Chemical Society·Marta TothSergei Vakulenko
Jun 28, 2006·Antimicrobial Agents and Chemotherapy·Eric SauvagePaulette Charlier
Oct 16, 2004·Expert Review of Anti-infective Therapy·Thomas D Gootz
Oct 24, 2012·Acta Crystallographica. Section D, Biological Crystallography·Yu-He LiangXiao-Dong Su
May 11, 2010·Journal of Molecular Biology·Julien DelmasRichard Bonnet
Jan 7, 2022·Journal of Biomolecular Structure & Dynamics·Vidhu AgarwalPritish Varadwaj

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